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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 7, 2025; 31(45): 113060
Published online Dec 7, 2025. doi: 10.3748/wjg.v31.i45.113060
Published online Dec 7, 2025. doi: 10.3748/wjg.v31.i45.113060
Clinical characteristics and risk factors of refractory gastroesophageal reflux disease: A multicenter cross-sectional study
Nan Zhang, Yi Wang, Shuang-Shuang Fang, Ming Han, Qin-Wei Zheng, Ying-Ying Zhu, Meng-Yuan Zhang, Jing-Jing Li, Lin-Xuan Cui, Jin-Li Tian, Yu-Hai Deng, Sheng-Liang Zhu, Hong-Wei Wang, Sheng-Quan Fang, Department of Gastroenterology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
Hong-Mei Ni, Department of Basic Theory of Traditional Chinese Medicine, College of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
Li Zhou, Department of Gastroenterology, Xuhui District Xietuo Subdistrict Community Health Service Center, Shanghai 200030, China
Guang-Liang Zuo, Department of Gastroenterology, Linfeng Road Sub-District Community Health Service Center of Jing’an District, Shanghai 200040, China
Tian-Sheng Huang, Department of Gastroenterology, Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai 200050, China
Qi Liao, Department of Gastroenterology, Shanghai Construction Hospital, Shanghai 200086, China
Xiu-Qing Li, Department of Gastroenterology, Third People’s Hospital of Chongming District, Shanghai 202150, China
Ying-Ying Shang, Department of Gastroenterology, Jiading District Traditional Chinese Medicine Hospital, Shanghai 201899, China
Yong-Jun Wang, Department of Gastroenterology, Yangpu District Traditional Chinese Medicine Hospital, Shanghai 200093, China
Yun Tian, Department of Gastroenterology, Tianshan Traditional Chinese Medicine Hospital of Changning District, Shanghai 200051, China
Ling-Yu Ge, Department of Gastroenterology, Community Health Service Center of Nanxiang Town, Jiading District, Shanghai 201800, China
Hai-Qiong Han, Department of Gastroenterology, Jiangqiao Town Community Health Service Center, Jiading District, Shanghai 201800, China
Wei-Min Hu, Department of Gastroenterology, Yuanpu District Yinxing Community Health Service Center, Shanghai 200090, China
Yi Jiang, Department of Gastroenterology, Sichuan North Road Street Community Health Service Center, Shanghai 200080, China
Ya-Juan Li, Department of Gastroenterology, Lianyang Community Health Service Center of Pudong New Area, Shanghai 201200, China
Xiang Mao, Department of Gastroenterology, Hongkou District Jiaxing Road Sub-District Community Health Service Center, Shanghai 200080, China
Li-Hong Yang, Department of Gastroenterology, Yuyuan Sub-District Community Health Service Center of Huangpu District, Shanghai 200001, China
Jun-Min Yao, Department of Gastroenterology, Yangpu District Wujiaochang Community Health Service Center, Shanghai 200090, China
Xin Zheng, Department of Gastroenterology, Quyang Road Sub-District Community Health Service Center of Hongkou District, Shanghai 200080, China
Co-first authors: Nan Zhang and Yi Wang.
Co-corresponding authors: Hong-Wei Wang and Sheng-Quan Fang.
Author contributions: Zhang N, Wang Y, Zhu SL, Ni HM, Wang HW and Fang SQ contributed to the conceptualization and supervision of the manuscript; Zhang N was involved in the validation of this study; Zhou L, Zuo GL, Huang TS, Liao Q, Li XQ, Shang YY, Wang YJ, Tian Y, Ge LY, Han HQ, Hu WM, Jiang Y, Li YJ, Mao X, Yang LH, Yao JM and Zheng X contributed to the process of patients inclusion and data collection; Zhang N, Wang Y, Fang SS, Han M, Zheng QW, Zhu YY, Zhang MY, Li JJ, Cui LX, Tian JL and Deng YH participated in the data curation; Zhang N and Wang Y contributed to the statistical analysis and writing of the original manuscript.
Supported by the National Key Research and Development Program Project, No. 2024YFC3505303; Flagship Department Construction Project of Traditional Chinese Medicine and Western Medicine Collaboration of the State Administration of Traditional Chinese Medicine, No. 2024-2027; Shanghai Municipal Government’s Three-Year Action Plan for Accelerating the Inheritance and Innovation of Traditional Chinese Medicine, No. 2025-2027-(1-1-2); Zhu Sheng-Liang National Prestigious Chinese Medicine Experts Inheritance Workshop Construction Project National Traditional Chinese Medicine Human Education Letter (2022), No. 75; Shanghai Municipal Government Three-Year Action Plan for Traditional Chinese Medicine Key Project, No. ZY (2021-2023)-0302; Shanghai Municipal Health Commission Clinical Specialties, No. 202140171; Natural Science Foundation of Shanghai Science and Technology Commission, No. 20ZR1459300; Shanghai Municipal Hospital Gastroenterology Clinical Competence Improvement and Advancement Specialist Alliance, No. SHDC22024302; Shanghai University of Traditional Chinese Medicine Affiliated Yueyang Integrated Traditional and Western Medicine, Hospital Translational Medicine Research Fund, No. 2024YJJB14; and Training Program for High-caliber Talents of Clinical Research at Affiliated Hospitals of Shanghai University of Traditional Chinese Medicine.
Institutional review board statement: The Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Affiliated to Shanghai University of Traditional Chinese Medicine, approved the study (Ethical Review No. 2023-196).
Informed consent statement: Informed consent was obtained from all participants in this study.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
STROBE statement: The authors have read the STROBE Statement—a checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-a checklist of items.
Data sharing statement: The data supporting the findings of this study are available from the corresponding author upon reasonable request.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Sheng-Quan Fang, MD, Professor, Department of Gastroenterology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No. 110 Ganhe Road, Hongkou District, Shanghai 200437, China. fsq20032003@163.com
Received: August 14, 2025
Revised: September 16, 2025
Accepted: October 23, 2025
Published online: December 7, 2025
Processing time: 111 Days and 17.7 Hours
Revised: September 16, 2025
Accepted: October 23, 2025
Published online: December 7, 2025
Processing time: 111 Days and 17.7 Hours
Core Tip
Core Tip: Refractory gastroesophageal reflux disease (GERD) represents a clinically challenging subtype of GERD that remains poorly understood. This cross-sectional study examined data from 256 patients with refractory GERD and 655 patients with non-refractory GERD to identify clinical characteristics and potential risk factors. The results indicate that prolonged disease duration, anxiety, and insufficient physical activity are independent risk factors for refractory GERD. Furthermore, age, overeating, esophageal chest pain, sensation of pharyngeal obstruction, and constipation showed strong correlations with refractory GERD. These findings underscore the presence of distinct, complex pathophysiological mechanisms and clinical features in refractory GERD, along with the role of psychological factors, providing useful insights for long-term management and treatment strategies for refractory GERD.